We plan to continue our studies on the interferon system: its biochemistry, the mechanism by which it impairs virus replication and its effects on cellular gene expression. Specifically we propose to isolate, characterize and study the physiological role of the agents which are apparently among the mediators of interferon action i.e.: 1) the pppA(2'p5'A)n synthetase; 2) the endonuclease activated by pppA(2'p5'A)n; 3) pppA(2'5'A)n; 4) The protein kinases(s) activated by double-stranded RNA; and 5) the inhibitor(s) of mRNA cap methylation. 6) We also wish to examine the ways in which interferon affects the "level" of the above agents and other gene products in cells i.e. the mechanism by which interferon affects cellular gene expression. 7) We plan to attempt to study the basis of the inhibition of cell multiplication by interferon. 8) We propose to explore aspects of the earliest phase of interferon action i.e. the interaction of interferons with the cell membrane. 9) The agents (listed in 1 to 3) as mediators of interferon action occur in the reticulocytes and other cells not treated with interferon. We will attempt to understand the rationale of their presence.